Toxicology of Petrogenic PAH in the Gulf Oil Spill. Petrogenic Polycyclic Aromatic Hydrocarbons (PAH) are believed to be the major long-term human health hazard associated with the gulf-oil spill due to chronic exposure through the food chain, dermal contact and possibly contaminated water. The overall theme of the GC-HARMS consortium is to understand and communicate the human health risks of exposure to potentially hazardous food-borne petrogenic PAH. Most of what we currently know about the toxicology of PAH has been learned from studying the representative PAH, benzo[a]pyrene (B[a]P) which is a multi-organ and multi-species carcinogen and known human carcinogen. As a result, US-EPA includes B[a]P as one of its 16 priority PAH pollutants that it monitors in the food chain. However, B[a]P and the other priority PAH pollutants are not major components of crude-oil. In fact, the PAH composition of crude oil is complex and contains PAH mixtures for which we have little to know toxicological data. Thus risk assessment based on the B[a]P toxicity equivalency quotient (TEO) cannot be performed in the absence of further information. Two classes of petrogenic PAH are abundant and these are the extensively alkylated PAH and the oxygenated PAH associated with crude oil weathering. We hypothesize that alkylated PAH will be hydroxylated on their alkane side chains, followed by activation via sulfation. We also hypothesize that the oxygenated PAH may mediate their effects via extensive redox-cycling leading to the generation of reactive oxygen species (ROS). Our goal is to characterize the metabolism and toxicity of the petrogenic PAH species. Our laboratories have extensive experience in studying PAH-metabolism, PAH-toxicity, and oxygenated PAH using state-of-the art methodologies. Our specific aims are as follows. Aim 1 will determine the relative potency of selected alkylated and oxygenated petrogenic PAH and PAH extracts using cell-based exposure and effect biomarkers (Elferink). Aim 2 will elucidate the metabolism of representative alkylated and oxygenated petrogenic PAH (Penning). Aim 3 seeks to determine whether oxygenated petrogenic PAH causes oxidative stress injury (Penning), and Aim 4 will determine the mutagenicity of alkylated and oxygenated petrogenic PAH (Penning).